Brucella infects a significant number of people and livestock in developing countries and infects wild as well as domestic animals in the United States. In addition, Brucella is a potential biowarfare agent, having been experimentally weaponized; strains of Brucella have been constructed with resistance to multiple antibiotics used to treat the disease. These strains pose a significant morbidity and mortality threat to exposed personnel. Brucellosis symptoms include recurring fever, chills and anxiety. Even though the disease is rarely fatal, once well established, the disease is difficult to treat since the bacteria reside in the bone marrow.
The Department of Bacterial Diseases at the Walter Reed Army Institute of Research is developing live, attenuated Brucella mutants as vaccines to protect military troops against infection with Brucella, an incapacitating biowarfare threat agent. Brucella, a slow-growing, facultative intracellular bacterial parasite of macrophages, causes systemic febrile illness in humans. Its lipopolysaccharide (LPS) is a potent immunomodulator that is being explored as a potential adjuvant to elicit immunity against HIV proteins.
A live attenuated Brucella vaccine was developed by the inventors, as described in U.S. Pat. No. 6,444,445 (issued Sep. 3, 2002), the entire contents of which are incorporated herein by reference. This vaccine utilized a strain of Brucella having a non-reverting deletion in the rfbU gene (now generally referred to in the art as the wboA gene). The result was a live Brucella vaccine that does not cause seroconversion in a vaccinee exposed thereto.